黏膜疫苗传递系统的研究进展

黏膜疫苗能同时诱导系统和局部黏膜免疫应答,是预防感染性疾病最理想的一类疫苗.但黏膜疫苗存在两大障碍:抗原无效摄取和难以引发有效免疫反应.因此,研发新型黏膜疫苗传递系统必须要克服这些障碍.本文综述了黏膜免疫的作用机制、黏膜疫苗的特点及其传递系统的研究现状.     

流感疫苗黏膜佐剂研究进展

当前流感疫苗主要为肌内注射灭活疫苗和滴鼻减毒活疫苗.对于预防呼吸道传播的流感,抗原特异性黏膜免疫应答非常重要.现有资料显示,两种疫苗都存在不可避免的局限性,为解决这个问题,需要对黏膜佐剂流感疫苗进行深入的研究.此文对进入临床试验的流感疫苗黏膜佐剂进行综述.     

抗HIV黏膜免疫评价方法研究进展

黏膜是人类免疫缺陷病毒(human immunodeficiency virus,HIV)侵人机体最主要的途径之一,评价黏膜免疫应答对评价HIV疫苗效果至关重要.用于检测不同动物模型和人体黏膜免疫应答的方法不尽相同,包括黏膜取样方法、样品保存、黏膜标记物种类和检测等方面,因此,建立统一的抗HIV黏膜免疫应答评价系统具有...     

小鼠重组乙肝病毒表面抗原鼻腔黏膜免疫效果评价

目的 评价小鼠重组乙肝病毒表面抗原(HBsAg)鼻腔黏膜免疫效果,寻找非注射乙肝免疫途径.方法 Balb/c小鼠分别经鼻腔、舌下及肌注给予重组HBsAg免疫3次,以支气管肺泡灌洗液(BALF)和血清抗HBsAg抗体水平评价3种途径的免疫效果.结果 经鼻腔免疫小鼠BALF可检测到IgA抗体,提示产生黏膜免疫:与肌注免疫类似,经鼻腔免疫小鼠血清IgG滴度大于1:500,提示产生体液免疫.结论 重组HBsAg经鼻腔免疫小鼠可同时产生体液免疫和黏膜免疫,提示鼻腔黏膜免疫可能是有效的非注射乙肝免疫途径.     

内镜下黏膜剥离术治疗食管黏膜层及黏膜下层病变临床分析

目的 探讨内镜下黏膜剥离术(ESD)治疗食管黏膜层及黏膜下层病变的有效性及安全性.方法 我中心2008年6月～2011年2月对26例食管黏膜层及黏膜下层病变进行了ESD,术后3个月行胃镜检查随访.结果 病变位于黏膜层11例,平均直径为14.8 mm(11～32 mm),其中Barrett食管伴急、慢性炎症4例,黏膜组织...     

黏膜免疫佐剂及抗原呈递系统研究现状

经济、稳定、高效的黏膜疫苗是目前疫苗研究的新方向,其中,黏膜免疫佐剂及抗原呈递系统是黏膜疫苗研究的重点之一,安全有效的免疫佐剂及抗原呈递系统可大大提高黏膜免疫的效果.       

基因疫苗微粒系统黏膜免疫的研究进展

微粒系统作为一种基因疫苗的黏膜免疫递送系统,能够增强免疫效果,具有同时诱导系统免疫应答和黏膜免疫应答、产生共同黏膜免疫应答、增加病人的顺应性、降低疫苗推广成本等优点.文章综述微粒系统增强基因疫苗黏膜免疫效果的机制、常见的微粒系统、载体材料以及优化微粒系统的研究进展.     

CT-2＊作为佐剂诱导的对多肽抗原的黏膜和全身性细胞免疫应答

很多病毒通过吸附黏膜而感染宿主，因此，直接靶向黏膜表面的接种策略将有助于预防病毒感染。黏膜途径免疫的主要问题是免疫效果和／或黏膜的抗原吸附差，甚至引起宿主的免疫耐受。因此，运用与黏膜表面相容的佐剂来加强抗原的免疫原性至关重要。已有很多细菌毒素被用作黏膜佐剂，此项研究检测了2个密码予突变的霍乱毒素（CT2＊，无ADP核糖基化活性和毒性）的黏膜佐剂作用。     

艾滋病黏膜疫苗的现状及未来方向

人免疫缺陷病毒(HIV)通过黏膜表面进行传播,因此,诱导抗病毒黏膜传播的保护作用至关重要,作者就研制艾滋病黏膜疫苗所涉及的现行策略、黏膜细胞毒性T淋巴细胞(CTL)在控制猴免疫缺陷病毒(SIV)/HIV感染中的效力、细胞因子和佐剂在增强抗HIV抗原的黏膜效应子及记忆性CTL应答中的相互作用等问题进行扼要阐述.     

黏膜免疫佐剂及抗原呈递系统研究现状

经济、稳定、高效的黏膜疫苗是目前疫苗研究的新方向，其中，黏膜免疫佐剂及抗原呈递系统是黏膜疫苗研究的重点之一，安全有效的免疫佐剂及抗原呈递系统可大大提高黏膜免疫的效果。     

oesophageal mucosal resistance

The human oesophagus is lined by a moist, partially keratinized, stratified squamous epithelium, one important property of which is to serve as a barrier between the outside (luminal) world and the internal world of the organism. This phenomenon in clinical parlance is known as 'oesophageal mucosal resistance'. This article details the structure and functions of the oesophageal mucosa that contribute to its defence against injury upon exposure to refluxed gastric acid.     

Gastric mucosal blood flow in ethanol-induced mucosal damage in the rat

Gastric mucosal blood flow in ethanol-induced mucosal damage was studied in urethane-anaesthetised rats by reference to ¹⁴C-aminopyrine clearance in the gastric mucosa. Irrigation of the stomach with 30% ethanol in acid saline (100 mM HCl plus 50 mM NaCl) for 40 min broke the gastric mucosal barrier, as indicated by an increased outflow of Na⁺ and K⁺ ions and back-diffusion of H⁺ ions. Gastric mucosal blood flow also increased about 2-fold, decreasing after cessation of ethanol irrigation along with the net ion fluxes. The increase in gastric mucosal blood flow occasioned by 10, 20 and 30% ethanol in acid saline was directly proportional to the net fluxes of H⁺, Na⁺ and K⁺ ions. When the stomach was irrigated with 30% ethanol in a less acid medium (10 mM HCl, 90 mM choline chloride plus 50 mM NaCl) there was still a significant increase in the outflow of Na⁺ and K⁺ ions, but only a slight back-diffusion of H⁺ ions. During this low rate of acid back-diffusion 30% ethanol reduced gastric mucosal blood flow by about 50%. The results suggest that ethanol-induced mucosal damage in the rat is associated with an increase in gastric mucosal blood flow only if combined with back-diffusion of H⁺ ions.     

The gastric mucosal barrier

Most gastroduodenal ulcer disease results from a weakness in the normal gastric mucous barrier against the penetration of acid secreted by the stomach. Based on meticulous and insightful research, the distinguished physiologist Franklin Hollander hypothesized that the stomach is protected against its own acid secretion by a dynamic two-component mucus-mucosal barrier. Hollander and his co-workers defined the physical and chemical characteristics of the mucus components of this barrier, as well as the defense provided by the surface epithelial cell layer, which he viewed as the second line of defense (the second component). Barrier investigators at Mount Sinai demonstrated the effects of impairment of barrier function with resultant increased back-diffusion of acid, and they defined the consequences of this acid penetration into the gastric epithelium. The contribution of these workers included important observations on the natural impermeability of the gastric corpus and fundus as well as the normally increased permeability of the antrum. They also presented evidence on the role of bile in duodenogastric reflux in gastric ulcer disease and the presence of impaired barrier function in patients with gastric ulcer and pernicious anemia. Further studies included demonstration that stress and carcinogens could disrupt the gastric mucosal barrier. Disruption of the barrier, in turn, was shown to allow carcinogenesis to occur by permitting the absorption of certain carcinogens which otherwise are warded off by the barrier. The Hollander two-component gastric mucosal barrier hypothesis has, in recent years, been increasingly validated by experimental data coming from other laboratories.     

Hydrogels in mucosal delivery

The concept of mucoadhesion and the molecular design requirements for the synthesis of mucoadhesive agents are both well understood and, as a result, hydrogel formulations that may be applied to mucosal surfaces are readily accessible. Nanosized hydrogel systems that make use of biological recognition or targeting motifs, by reacting to disease-specific environmental triggers and/or chemical signals to affect drug release, are now emerging as components of a new generation of therapeutics that promise improved residence time, faster response to stimuli and triggered release.     

Uniqueness of the mucosal immune system for the development of prospective mucosal vaccine

The mucosal immune system acts as the first line of defense against microbial infection through a dynamic immune network based on innate and acquired mucosal immunity. To prevent infectious diseases, it is pivotal to develop effective mucosal vaccines that can induce both mucosal and systemic immune responses, especially secretory IgA (S-IgA) and plasma IgG, against pathogens. Recent advances in medical and biomolecular engineering technology and progress in cellular and molecular immunology and infectious diseases have made it possible to develop versatile mucosal vaccine systems. In particular, mucosal vaccines have become more attractive due to recent development and adaptation of new types of drug delivery systems not only for the protection of antigens from the harsh conditions of the mucosal environment but also for effective antigen delivery to mucosa-associated lymphoid tissues such as Peyer's patches and nasopharynx-associated lymphoid tissue, the initiation site for the induction of the antigen-specific immune response. In this review, we shed light on the dynamics of the mucosal immune system and recent advances toward the development of prospective mucosal antigen delivery systems for vaccines.     

Regulation of airway mucosal hydration

Ion channels control the hydration status of the airway epithelium through apical anion secretion and cation absorption, which is accompanied by osmotically obligated water. The key channels in this process are the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), which is principally responsible for Cl(-) secretion by airway epithelial cells, and the epithelial Na(+) channel (ENaC), which is responsible for the absorption of Na ions. In CF, defective CFTR-mediated Cl(-) secretion and an accompanying upregulation in ENaC-mediated Na absorption results in a reduction in airway surface liquid volume, leading to poorly hydrated mucus and impaired mucociliary clearance. Restoration of normal airway hydration by modulation of ion channel activity represents an important therapeutic strategy for CF. CFTR corrector and potentiator compounds are being developed with the aim of recovering normal Cl(-) secretion. Ca(2+)-activated Cl(-) channels (CaCCs) are expressed by the respiratory epithelia and are reported to be functionally upregulated in CF and offer a 'surrogate' pathway for Cl(-) secretion. TMEM16A has recently been described as a CaCC in the airway epithelium and, as such, represents an alternative target for restoring Cl(-) secretion in CF. An alternative therapeutic strategy for CF is to inhibit ENaC, thereby blocking excessive Na absorption. This can be achieved by direct blockade of ENaC or inhibition of the channel-activating proteases (CAPs), whose activity regulates ENaC function. This review will describe the regulation of airway mucosal hydration by ion channels and the efforts currently underway to restore normal mucosal hydration in disease patients by modulating the function of these channels.     

Chitosan for mucosal vaccination.

The striking advantage of mucosal vaccination is the production of local antibodies at the sites where pathogens enter the body. Because vaccines alone are not sufficiently taken up after mucosal administration, they need to be co-administered with penetration enhancers, adjuvants or encapsulated in particles. Chitosan easily forms microparticles and nanoparticles which encapsulate large amounts of antigens such as ovalbumin, diphtheria toxoid or tetanus toxoid. It has been shown that ovalbumin loaded chitosan microparticles are taken up by the Peyer's patches of the gut associated lymphoid tissue (GALT). This unique uptake demonstrates that chitosan particulate drug carrier systems are promising candidates for oral vaccination. Additionally, after co-administering chitosan with antigens in nasal vaccination studies, a strong enhancement of both mucosal and systemic immune responses is observed. This makes chitosan very suitable for nasal vaccine delivery. In conclusion, chitosan particles, powders and solutions are promising candidates for mucosal vaccine delivery. Mucosal vaccination not only reduces costs and increases patient compliance, but also complicates the invasion of pathogens through mucosal sites.     

Neuropeptides and gastric mucosal homeostasis

The role of central nervous system (CNS) in regulation of gastric function has long been known. The dorsal vagal complex (DVC) has an important role in regulation of gastric mucosal integrity; it is involved both in mucosal protection and in ulcer formation. Neuropeptides have been identified in DVC, the origin of these peptides are both intrinsic and extrinsic. Neuropeptides are localized also in the periphery, in afferent neurons. The afferent neurons also have efferent-like function in the gastroinetestinal tract, and neuropeptides released from the peripheral nerve endings of primary afferent neurons can induce gastric mucosal protection. Centrally and /or peripherally injected neuropeptides, such as amylin, adrenomedullin, bombesin, cholecystokinin, neurotensin, opioid peptides, thyreotropin releasing hormone and vasoactive intestinal peptide, influence both the acid secretion and the gastric mucosal lesions induced by different ulcerogens. The centrally induced gastroprotective effect of neuropeptides may be partly due to a vagal dependent increase of gastric mucosal resistance to injury; activation of vagal cholinergic pathway is resulted in stimulation of the release of mucosal prostaglandin and nitric oxide. Furthermore, release of sensory neuropeptides (calcitonin gene-related peptide, tachykinins) from capsaicin sensitive afferent fibers are also involved in the centrally induced gastroprotective effect of neuropeptides.     

内镜下黏膜切除术治疗消化道黏膜病变疗效分析

目的：探讨内镜下黏膜切除术(EMR)对消化道黏膜病变的临床应用价值。方法对137例内镜下黏膜切除术治疗消化道黏膜病变患者的临床资料进行回顾性分析。结果137例患者共计189处病灶,181处病灶予以完整切除,转外科手术5例;活动性出血21例,均内镜下成功止血,无穿孔发生。结论 EMR是治疗消化道黏膜病变安全、有效、实用的内镜诊疗技术。